1A-O1-1705 PDF
A Large Scale Human Plasma Peptidomics
Serum and plasma contain a large number of different types of proteins and peptides, which can provide valuable information about the numerous processes that take place within the body. However, detailed analyses of proteins and peptides in serum and plasma are still challenging because of the presence of many high-abundance proteins, the large dynamic range of protein and peptide concentrations, rendering the extremely high complexity of the serum/plasma proteome. In particular, detailed analysis and identification of native peptides is extremely difficult due to the tremendous variety of cleavage possibilities and posttranslational modifications, which results in extremely high complexity. Herein we have improved our ultrahigh-yield method to extract and analyze plasma low-molecular-weight peptides, and initiated the large-scale sequencing of circulating native peptides using less than 0.2 ml of human plasma. This initial plasma peptidomic analysis successfully identified more than 18,500 distinct native peptides with false discovery rate (FDR) 1%. Among those identified were 11 well-known bioactive/biomarker peptides, cleaved products of many other bioactive peptide precursors, high-abundance proteins and cellular component proteins. Our results constitute a non-biased representation of circulating native peptide population in humans and are now engendering endogenous “orphan ligands” library.